The antiviral and anti-tumor activity of various interferons is currently being explored. Recently, it has been contemplated to generate hybrid interferons that are not naturally occurring in nature. Such a procedure is shown in U.S. Pat. No. 4,414,150, issued: Nov. 8, 1983.
This invention has advanced the current techniques into further unchartered areas. Rather than dealing with known "whole" segments of interferon, this invention has hybridized, abbreviated, or shortened segments or "sub-segments."
We have found that when the hybrid is formed specifically corresponding to a truncated alpha-2 segment and an alpha-1 segment, the resultant species has a very desirable biological profile.
As is well recognized in the art, the initiation codon ATG has a second meaning corresponding to the presence of the amino acid methionine at the first amino acid in a chain of amino acids comprising a protein. Sometimes the host will cleave this amino terminal methionine off the protein and sometimes not. Our invention contemplates both species. In the former case it will have 161 amino acids and start with glutamine (at the amino terminus) and when the methionine is not cleaved, the resultant protein will have 162 amino acids and the first residue will be methionine.
The new abbreviated interferon species engineered by this invention features a "sub-segment" defined as a delta-4 alpha-2 (Bgl II-1) derived from an alpha-2 sequence, that is joined to a segment defined as (Bgl II) alpha-1 derived from an alpha-1 sequence.
To our pleasant surprise, the above protein features selectively heightened antiviral and anti-tumor activity.
The present invention is characterized as having an antiviral activity of at least 1.times.10.sup.7 units/mg as determined by the cytopathic effect-inhibition assay employing EMC virus and human foreskin cells (FS-71) performed essentially as described in a publication by Familletti, et. al. (Reference 1), using as a standard the NIH/WHO uncloned leukocyte interferon standard 69/19.